Objectives

NEPHROTIC SYNDROME IN
PREGNANCY

Anne-Marie Ct, MD, MHSc

NASOM Annual Conference
October 20th 2012, Qubec

At the end of the session, the participant

will be able to:
Counsel their patient with nephrotic
syndrome about the risks and
complications of pregnancy
Follow and manage the principal
complications (oedema, hypertension,
thromboembolic risk, etc.)

Detection of nephrotic range

proteinuria in pregnancy
Routine antenatal urine dipstick screening
in an asymptomatic woman
Focused work-up in specific high-risk
population
known renal disease or risk factors for renal
disease (e.g.diabetes)
hypertensive: to rule out preeclampsia or for
baseline work-up of pre-existing hypertension

New-onset oedema investigation

Prevalence: not3 well reported

Outline
1) GENERAL ISSUES
2) IMPACT OF NEPHROTIC
SYNDROME IN PREGNANCY
3) MANAGEMENT CHALLENGES
DURING PREGNANCY
4) POSTPARTUM MANAGEMENT

Physiology and definitions

GENERAL ISSUES
FOR NEPHROTIC SYNDROME
Physiology/definitions
Detection
Causes
Assessment

Nephrotic syndrome in pregnancy

Significant proteinuria
= 150 300mg/d in pregnancy
glomerular and tubular proteinuria

Most common cause = preeclampsia

After 20wks GA :
R/O preeclampsia until proven otherwise

Nephrotic syndrome
>3g/d, albumin < 30g/L, oedema
hypercholesterolemia, lipiduria

Nephrotic range proteinuria

>3g/d, usually glomerular proteinuria
7

proteinuria with hypertension:

Hematuria, red cell casts, creatinine
Symptoms and signs of systemic disease
(preeclampsia mimickers)
8

Maternal/fetal considerations

Causes of Proteinuria

Maternal

Glomerular diseases
Preeclampsia**
Diabetes (type 1 and 2)*
IgA GN*
Focal and segmental glomerulosclerosis
(FSGS)*
Lupus nephritis

IMPACT OF NEPHROTIC
SYNDROME IN PREGNANCY
Maternal/fetal considerations
Preconception counselling

10

Maternal/fetal considerations

11

Maternal/fetal considerations

Maternal:

Fetal

Risks

Fetal growth restriction

vary according to associated conditions

Acute kidney injury

Chronic renal failure / ESRD
Gestational hypertension
Preeclampsia / severe preeclampsia
Maternal renal and life expectancy

Modified by acute renal complications in

pregnancy / postpartum

Prematurity
Stillbirth
Fetal anasarca
Polyhydramnios

Less data with amiloride

Statins
Immunosuppressives

e.g. minimal change, FSGS or membranous GN

15

Clinical issues in the management of

nephrotic syndrome during pregnancy

MANAGEMENT CHALLENGES
DURING PREGNANCY
Clinical issues

Less data for renal diseases

16

Antiproteinuric drugs cessation

Physiology of pregnancy

14

ASA for prevention of preeclampsia

Nephrotic syndrome
Renal function
Blood pressure

Genetic transmission: rare

AZA, cyclosporine, tacrolimus

MMF, CYC

Biphosphonate / Others

Proteinuria likely to increase

Preconception counselling

Furosemide / HCTZ

Preconception counselling

Renal disease controlled

most likely related to reduced utero-placental

perfusion / low colloid osmotic pressure and reduction
in effective blood volume

Drugs
Antiproteinuric
ACEI/ARB/anti-aldo

12

Maternal condition

13

Conditions to consider:
Preexisting renal insufficiency
Preexisting hypertension
Type of underlying renal disease
Concomitant maternal comorbidities

17

Oedema
Blood pressure control
Acute kidney injury
Thrombotic risk
Anemia
Malnutrition
Vitamin D deficiency
Risk of infection
Timing of delivery
18

Management challenges

Management challenges

Oedema: strategies

Oedema : Monitoring of diuretic treatment:

Stockings / Leg elevation

Salt restriction <100mmol/day (2.3g of sodium)
Water restriction 1.5L/day
Diuretics: aim at a negative balance of no more
than 0.5-1.0 L/d

Response to diuretics:

Furosemide (oral or iv): start with lower dose 5-10 mg (to

prevent acute intravascular dehydration and
hypotension; see below for monitoring) and titrate
according to clinical response (diureses, weight, BP);
use shorter intervals (e.g. q 6-8hr)
Thiazide if resistance to loop diuretic

Colloids

Daily weight and input/output, BP and heart rate when

adjusting treatment

Metabolic disturbances:
electrolytes (sodium, potassium, magnesium, calcium)
diuretic-induced alcalosis (normal bicarbonate levels in
pregnancy around 18-20meq/L)

Renal function
serum creatinine and urea; 24hr creatinine clearance

24hr urinary sodium excretion

Management challenges
Blood pressure control
BP goal 110-140/80-90
no data on best threshold
balance between maternal BP and
uteroplacental blood flow
Antihypertensives drugs
When hypervolemia present:
salt and water restriction / diuretics

may be useful to assess resistance to diuretics (aim for

sodium excretion >100mmol/day (2.3g/day)

Controversial / use in exceptional circumstances

19

Antihypertensive drugs in nephrotic

range proteinuria during pregnancy
Choices most frequently used for the HDP in Canada (including
proteinuric preeclampsia):

20

Antihypertensive drugs in nephrotic

range proteinuria during pregnancy
Other choices:

labetalol easy to titrate; other betablockers OK (avoid atenolol)

nifedipine outside pregnancy, not first choice in proteinuric

diltiazem use to decrease proteinuria outside pregnancy; very

small study in pregnant women with renal disease (N=7); good
choice in 2nd- 3rd trimester (caution in 1st trimester as security not
yet established). Avoid to use concomitantly with betablockers

renal disease as dihydropyridine calcium channel blockers may

increase proteinuria by preferential dilation of afferent arteriole;
however remain an alternative when needed for BP control

hydralazine and others

21

Management challenges
Acute kidney injury (AKI)
Prerenal:
decreased oncotic pressure
aggressive use of diuretics
especially when strict water and salt restrictions are
applied (be careful with in-hospital versus outpatient
modification in lifestyle and intake

diarrhea, nausea and vomiting

infection and sepsis

methyldopa if already anemic, beware of hemolytic anemia and

warm antibodies

22
SOGC HDP
guidelines 2008

Management challenges
Acute kidney injury (AKI)
Renal:
underlying renal disease progression
preeclampsia
acute tubular necrosis
acute interstitial nephritis
other
Post renal:
ureteral compression from gravid uterus
especially in multiple pregnancy or polyhydramnios

23

Management challenges
Thrombotic risk
Contributing factors

Management challenges
Thrombotic risk

prothrombotic state of pregnancy

urinary loss of anticoagulant proteins

Other predisposing conditions and risk

factors

e.g.antithrombin III

e.g. known thrombophilia, obesity,

immobilisation due to obstetrical condition

hepatic synthesis of clotting factors

intravascular hypovolemia

Threshold for prophylaxis

interstitial fluid leak

Salt / water restriction / use of diuretics

inflammation
decreased mobilisation
25

24

when severe peripheral edema

26

No consensus
? Proteinuria >3-3.5g/d
? antithrombin III below normal
? serum albumin <20-25g/L
<28g/L Lionaki CJASN 2012
27

Management challenges

Anemia in nephrotic syndrome

Thrombotic risk
Prophylaxis / anticoagulation
same as for other medical conditions

choice of anticoagulant agent

LMWH vs UFH

dosing regimens / level of anticoagulation

prophylactic vs. intermediate vs. therapeutic
n.b. LMWH not recommended when eGFR<30ml/min

Contributing causes
Physiologic anemia of pregnancy
Inflammation of acute and/or chronic disease
Decreased intestinal absorption of iron, B12 and
folate
Renal loss of transferrin
Decreased erythropoietin production if GFR
significantly decreased (usually<50ml/min)
Gastro-intestinal spoliation and other sources of
bleeding

28

29

Management challenges

Management challenges

Nutrition
Contributing factors

Vitamin D deficiency

Urinary loss of protein and other nutrients

Decreased intestinal absorption secondary to
intestinal wall edema
Inflammation leading to increased catabolism

Various regimens

Role of dietician

for severe deficiency (level <30)

e.g. 4000-5000 (up to 10 000) u/d for 2-4 wks,
maintenance dose 1000 u/d
adjust according to repeat calcium and vitamin D
serum levels (at least monthly)
n.b. correction of total calcium for decreased
albumin level or measure ionized calcium

Evaluation of intake/nutritional needs

Weight gain monitoring as surrogate of nutritional status
may be misleading when excess of edema

Anemia in nephrotic syndrome

Baseline work up
Blood smear, reticulocytes
Iron stores (total iron, saturation, ferritin)
Vitamin B12, folate
Inflammation markers (C reactive protein,
sedimentation rate)
Erythropoietin level when GFR <50ml/min
Hemolysis tests (haptoglobin, LDH, unconjugated
bilirubin)
Hemoglobinopathies screen (Hemoglobin
electrophoresis)

Adequate calcium intake (1200-1500mg/d)

30

Management challenges
Risk of infection
Increased urinary loss of immunoglobulins
No specific recommendation for nephrotic
syndrome
Prophylaxis treatment as needed
e.g. UTI

Vaccination
Timing of delivery

Parenteral nutrition not advocated (unproven benefits /

associated risks)
31

32

Postpartum management

POSTPARTUM MANAGEMENT
Clinical issues

Avoidance of NSAIDs ***

Oedema
spontaneous postpartum diuresis /
daily assessment / diuretics if
needed
Blood pressure control

33

Postpartum management
Acute kidney injury
Thrombotic risk
Thromboprophylaxis > 6 weeks
LMWH vs UFH vs coumadin

BP goal <130-140/80-90
antiproteinuric drugs as first choice
Unless AKI ; caution if prematurity

34

captopril, enalapril, spironolactone

compatible with breastfeeding
35

36

Postpartum management
Completion of renal investigation if
needed
Reassess appropriate medication for
specific renal disease

Conclusion

Questions

Key points
Nephrotic syndrome vs nephrotic range
proteinuria
Practical approach of the evaluation,
management and monitoring
Appropriate evaluation of the underlying renal
disease and its specific prognosis and treatments
Pluridisciplinary approach necessary to optimise
both maternal and fetal care and outcomes

37

38

39

Causes of Proteinuria

Glomerular diseases

Preeclampsia**
Diabetes (type 1 and 2)*
IgA GN*
Focal and segmental glomerulosclerosis
(FSGS)*
Lupus nephritis

Infection-related GN

40

ask
mom!

Current / recent symptoms:

oedema (onset, progression)
urinary symptoms (hematuria, frothy urine)
systemic symptoms, in particular suggestive of SLE,
infectious symptoms and risk factors for HIV/viral
hepatitis

Reflux nephropathy, congenital anomalies,

polycystic kidney disease, interstitial nephritis

urinary tract infections / vesicoureteral reflux

previous urinary tract investigations
nycturia
childhood GN
e.g. post-infectious GN, Henoch-Schonlein purpura,
minimal change

or not causing
nephrotic range proteinuria
43

Assessment of Proteinuria
Questionnaire (cont)

Birth weight / Prematurity / Perinatal complications

Infancy and childhood

1Rarely

minimal change, membranous, membranoproliferative,

other rare causes (e.g. amyloidosis, Fabry, Alport)

Birth

Renal diseases

exercise, fever/sepsis, congestive cardiac

disease, subarachnoid/intracranial hemorrhage,
seizures

Drugs-related GN
Other glomerular diseases in young
women:

42

Assessment of Proteinuria
Questionnaire

Transient causes

e.g. HIV, hepatitis B and C, post-streptococcal, visceral

abcess, endocarditis

41

Causes of Proteinuria
Other causes of proteinuria1

Causes of Proteinuria

Glomerular diseases

Drugs
prescription, over the counter, recreational

Familial history of renal diseases

44

45

Assessment of Proteinuria

Assessment of Proteinuria

Physical examination

Baseline work up: Urine

Vitals: Blood pressure, heart rate, O2 sat, T, weight, fluid

balance

Urine analysis / culture, urine sediment

Look for signs of:

Nephrotic syndrome
puffy eyelids, presence or absence of jugular vein
distension, lungs (crackles, pleural effusion), ascites
(more difficult with gravid uterus), presacral edema,
lower limb (severe edema and signs of deep vein
thrombosis)
Systemic diseases

Quantification of nephrotic range proteinuria

Urinary dipstick
Urinary spot protein/creatinine ratio
Urinary spot albumin/creatinine ratio
24hr urine collection

Assessment of Proteinuria
Baseline work up: Blood work

46

Assessment of Proteinuria

obtain also previous results

n.b. methods differ according

to local laboratories
47

Assessment of Proteinuria

Additional investigations (as indicated):

Additional investigations (as indicated)(cont):
Renal ultrasound
Renal lab : Bicarbonate, Mg, Ca, PO4, PTH, urea, uric
acid cholesterol
Systemic / renal disease markers:
C-Reactive protein, sedimentation rate
HbA1c / liver enzymes
C3, C4, ANA, DsDNA
viral serology (hepatitis B and C, HIV)
ANCA, anti-GBM, ASLO
49

Renal biopsy when diagnostic is needed for de novo

nephrotic syndrome
especially for initiation of treatment with
immunosuppressive drugs during pregnancy
decision according to gestational age, clinic and
balance of risks of procedure and maternal-fetal
risks/benefits ratio of diagnosis

50

CBC
creatinine,
Na, K, Cl
albumin
glucose

48